Research Overview

Our group integrates population and statistical genetics approaches into experimental analysis to understand molecular and evolutionary basis of human complex disease. The main areas of our research are i) Population genetics inference on the human history, ii) Estimating the tempo and mode of natural selection, and iii) Functional genomics on host-microbiome interactions.

Population genetics inference on the human history

Humans originated in Africa around 200 thousand years ago (kya) and expanded into the world 50 to 100 kya. The advance of genomic technologies, coupled with high-computing and powerful statistical approaches, has enhanced our understanding of the history of dispersal out of Africa. However, the peopling of East Asia and migration from Eurasia to the Americas still remain elusive. We are engaged in international projects to characterize genetic variation of Asians and Native Americans using whole-genome sequencing data and to apply statistical and population genetic modelling for the inferences on the complex evolutionary history including population demography (e.g., divergence, expansion, migration, and admixture) and adaptations to local environments (e.g., climates, diets, and pathogens).

Estimating the tempo and mode of natural selection

One of the fundamental questions about the adaptive history of a population is the time of onset of the selective pressure acting on beneficial alleles. Inferring this time in turn depends on the selection model. There are two main models of natural selection that drives adaptations to local environments: one is selection on new mutation and the other is selection on pre-existing (i.e., standing) genetic variation. An important difference between these two models is that under the selective sweep model the adaptive process must wait for the emergence of new beneficial mutations, while standing variants are immediately available as the source of beneficial alleles in the new environment. We develop a statistical framework to capture different population dynamics of beneficial alleles between the selection models and to understand the process of adaptation to new selective pressures.

Functional genomics on host-microbiome interactions

Changes in gut microbiota that maintain homeostasis of the mucosal surface are critical to the development of inflammatory bowel disease (IBD). At the same time, diet has a strong influence on the acquisition and structuring of the gut microbiome. The host immune system has been exposed to varying selective pressures as humans experienced shifts in dietary as well as pathogen pressures concomitant with the spread of agriculture, some of which may result in a failure to control misdirected immune response against intestinal bacteria nowadays. We employ quantitative genetics and population genetics approaches to understand mechanisms of host-microbiome cross-talk and impacts of human evolutionary history on dysregulation of the host immunity resulting in IBD.

Welcome to the Nakagome lab at School of Medicine, Trinity College Dublin. Our lab aims to understand how evolutionary pressures have shaped genetic variation in human populations and which to extent natural selection in the past impact on susceptibility to complex disease. Our research leverages experimental and computational tools and approaches, integrating them into a novel way to obtain genomic and functional profiles with cutting-edge high-throughput sequencing technologies and to create a powerful framework for unraveling biological roles of genetic variants in human disease and evolution.